Individuals diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) smoke more than the general population, initiate use at a younger age, and in general report more difficulty trying to quit. Several converging lines of work suggest that the high rates of smoking in patients with ADHD may be related to beneficial effects of nicotine on the requisite deficits in attention and other cognitive processes. As such, it has been proposed that smoking in ADHD patients is reinforced by these beneficial effects of nicotine. Surprisingly, however, and despite alarmingly high rates of smoking among this clinical population, little experimental work has been done to investigate possible mechanisms underlying this comorbidity. The overall goal of this project is to systematically assess the reinforcing effects of tobacco smoking in regular smokers with ADHD compared to those who do not have ADHD. Ninety-six adult smokers (48 with ADHD;48 free from any other psychiatric diagnoses) will participate in 3 separate experiments (32 subjects each) across the four-year period of the study. Each experiment will evaluate the reinforcing effects of smoking under different conditions (abstinent vs. satiated;high demand condition vs. low demand condition;stimulant medication vs. placebo) using a progressive-ratio task. This project will be the first to systematically evaluate smoking reinforcement in ADHD and non-ADHD smokers using rigorous laboratory techniques. The results of this project will not only identify potential mechanisms underlying the high rates of smoking on ADHD patients, but could also help explain elevated rates of other substance use problems in ADHD and other psychiatric co-morbidities. These experiments will also lead to subsequent grant applications to further explore basic neuropharmacological mechanisms associated with ADHD and smoking risk, as well as clinical projects to develop more effective interventions for nicotine dependence in this high-risk group. PUBLIC HEALTH RELEVANCE: This project is of considerable public health significance. Smoking is the leading cause of preventable death in the US and patients with ADHD smoke much more than people without ADHD. This project will help identify some of the reasons why people with ADHD smoke more and will potentially lead to better prevention and treatment programs.